Studies of human breast cancer patients have shown that the biologic behavior of breast cancer reflects an interaction between the aggressive potential of the cancer cells and the tumor-retarding influence of host's tumor-specific cell-mediated immunity (CMI). More recent in vitro studies of leukocytes from human breast cancer patients indicate that simultaneous CMI to autologous breast cancer and the major envelope glycoprotein (gp55) of RIII-murine mammary tumor virus is prognostically beneficial, as judged by postoperative survival characteristics. These findings suggest that gp55 could be of value in immunotherapy and immunoprophylaxis of breast cancer. However, ethical considerations dictate that a test of the therapeutic potential of gp55 be made on an experimental model before clinical trials in humans. The natural behavior and structural characteristics of canine mammary cancer suggest that the dog provides an appropriate model. Preliminary in vitro studies have demonstrated that some breast cancer dogs have CMI to their autologous cancer and/or reactivity to selected human cancers and to gp55. Conversely, some breast cancer patients have CMI to canine mammary carcinomas. The proposed study will seek to: (1) compare canine and human breast cancers in regard to structural, immunologic and biologic characteristics, and (2) determine whether therapeutic induction of gp55- and/or breast cancer-specific CMI in breast cancer dogs influences the biologic behavior of specifically characterized lesions.